11-47241041-T-G

Variant names:

• chr11-47241041-T-G
• rs11039143
• NM_001610.4:c.1139-792A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001610.4(ACP2):​c.1139-792A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 152,182 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.034 (124 hom., cov: 32)
• Consequence: ACP2 NM_001610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 2 publications found

Genes affected

ACP2 (HGNC:123): (acid phosphatase 2, lysosomal) The protein encoded by this gene belongs to the histidine acid phosphatase family, which hydrolyze orthophosphoric monoesters to alcohol and phosphate. This protein is localized to the lysosomal membrane, and is chemically and genetically distinct from the red cell acid phosphatase. Mice lacking this gene showed multiple defects, including bone structure alterations, lysosomal storage defects, and an increased tendency towards seizures. An enzymatically-inactive allele of this gene in mice showed severe growth retardation, hair-follicle abnormalities, and an ataxia-like phenotype. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism. [provided by RefSeq, Oct 2017]

ACP2 Gene-Disease associations (from GenCC):

• lysosomal acid phosphatase deficiency

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001610.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP2	NM_001610.4	MANE Select	c.1139-792A>C		intron	N/A	NP_001601.1
	ACP2	NM_001357016.2		c.1139-792A>C		intron	N/A	NP_001343945.1
	ACP2	NM_001302489.2		c.1055-792A>C		intron	N/A	NP_001289418.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP2	ENST00000672073.1	MANE Select	c.1139-792A>C		intron	N/A	ENSP00000500291.1
	ACP2	ENST00000256997.9	TSL:1	c.1139-792A>C		intron	N/A	ENSP00000256997.3
	ACP2	ENST00000672636.2		c.1139-792A>C		intron	N/A	ENSP00000500571.2

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 5212 AN: 152064 Hom.: 126 Cov.: 32

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.0426

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0321

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0342 AC: 5209 AN: 152182 Hom.: 124 Cov.: 32 AF XY: 0.0359 AC XY: 2673 AN XY: 74394

African (AFR) AF: 0.0228 AC: 948 AN: 41542

American (AMR) AF: 0.0166 AC: 253 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3470

East Asian (EAS) AF: 0.0419 AC: 217 AN: 5174

South Asian (SAS) AF: 0.121 AC: 586 AN: 4824

European-Finnish (FIN) AF: 0.0468 AC: 496 AN: 10594

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0377 AC: 2562 AN: 67986

Other (OTH) AF: 0.0322 AC: 68 AN: 2110

Alfa AF: 0.0337 Hom.: 55

Bravo AF: 0.0290

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.45
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11039143; hg19: chr11-47262592;